Juvenile idiopathic arthritis (JIA) (also known as juvenile rheumatoid arthritis (JRA), juvenile chronic polyarthritis, or Still's disease) is the most common rheumatic disease of childhood and an important cause of disability among children. JIA is an arthritis that causes joint inflammation and stiffness for more than 6 weeks in a child less than 16 years of age. In this disease, the immune system mistakenly targets the synovium. The synovium responds by making excess synovial fluid, which leads to swelling, pain and stiffness. The inflammation can then spread to the surrounding tissues, eventually damaging cartilage and bone. Other areas of the body, including the eyes, kidneys, lungs and heart, also may be affected by the inflammation.
Without treatment, JIA can interfere with a child's normal growth and development. Similar to the therapy of adult RA patients, disease-modifying antirheumatic drugs (DMARDs) and NSAIDs are often used to treat JIA. In recent years, tumor necrosis factor (TNF) has been identified as an important cytokine in the pathogenesis of JIA. Tumor necrosis factor has been implicated in the pathophysiology of juvenile arthritis, including juvenile idiopathic arthritis (Grom et al. (1996) Arthritis Rheum. 39:1703; Mangge et al. (1995) Arthritis Rheum. 8:211). Biologic response modifiers that inhibit TNF activity have become a new option for treatment of JIA, including infliximab, etanercept, and adalimumab (Ruperto et al. Clin Exp Rheumatol 2004; 22(4):522)).
Children present a unique challenge for dosing in general, as pediatric patient populations present a large range of weights and developmental ages. As such, treatment of JIA has often involved using a strict weight-based dosing scheme. For example, Ruperto et al. Arthritis Rheum. 2007 September; 56(9):2815-6 describes a combination therapy of infliximab and methotrexate for the treatment of JRA, where infliximab was administered at a dose of 3 mg/kg or 6 mg/kg. Similarly, etanercept may be used for the treatment of JIA and is delivered on a strict weight based dosing scheme, i.e., 0.8 mg/kg (see Enbrel® label; see also Lovell et al. Arthritis Rheum. 2003 January; 48(1):218-26).
For all patients, the goals of therapy are to decrease chronic joint pain and suppress the inflammatory process. Accomplishing these goals leads not only to improved short-term and long-term function but also to normal growth and development. JIA presents a unique challenge, not only for providing effective treatments but also for providing treatment regimens and agents which are appropriate for the young patient population associated with JIA.